White matter and hypoxic hypobaria in humans.

Occupational exposure to hypobaria (low atmospheric pressure) is a risk factor for reduced white matter integrity, increased white matter hyperintensive burden, and decline in cognitive function. We tested the hypothesis that a discrete hypobaric exposure will have a transient impact on cerebral physiology. Cerebral blood flow, fractional anisotropy of water diffusion in cerebral white matter, white matter hyperintensity volume, and concentrations of neurochemicals were measured at baseline and 24 hr and 72 hr postexposure in N = 64 healthy aircrew undergoing standard US Air Force altitude chamber training and compared to N = 60 controls not exposed to hypobaria. We observed that hypobaric exposure led to a significant rise in white matter cerebral blood flow (CBF) 24 hr postexposure that remained elevated, albeit not significantly, at 72 hr. No significant changes were observed in structural measurements or gray matter CBF. Subjects with higher baseline concentrations of neurochemicals associated with neuroprotection and maintenance of normal white matter physiology (glutathione, N-acetylaspartate, glutamate/glutamine) showed proportionally less white matter CBF changes. Our findings suggest that discrete hypobaric exposure may provide a model to study white matter injury associated with occupational hypobaric exposure.

Evaluation of the accuracy and precision of the diffusion parameter EStImation with Gibbs and NoisE removal pipeline.

This work evaluates the accuracy and precision of the Diffusion parameter EStImation with Gibbs and NoisE Removal (DESIGNER) pipeline, developed to identify and minimize common sources of methodological variability including: thermal noise, Gibbs ringing artifacts, Rician bias, EPI and eddy current induced spatial distortions, and motion-related artifacts. Following this processing pipeline, iterative parameter estimation techniques were used to derive diffusion parameters of interest based on the diffusion tensor and kurtosis tensor. We evaluated accuracy using a software phantom based on 36 diffusion datasets from the Human Connectome project and tested the precision by analyzing data from 30 healthy volunteers scanned three times within one week. Preprocessing with both DESIGNER or a standard pipeline based on smoothing (instead of noise removal) improved parameter precision by up to a factor of 2 compared to preprocessing with motion correction alone. When evaluating accuracy, we report average decreases in bias (deviation from simulated parameters) over all included regions for fractional anisotropy, mean diffusivity, mean kurtosis, and axonal water fraction of 9.7%, 8.7%, 4.2%, and 7.6% using DESIGNER compared to the standard pipeline, demonstrating that preprocessing with DESIGNER improves accuracy compared to other processing methods.

Using Behavioral Economics to Design Physician Incentives That Deliver High-Value Care.

Behavioral economics provides insights about the development of effective incentives for physicians to deliver high-value care. It suggests that the structure and delivery of incentives can shape behavior, as can thoughtful design of the decision-making environment. This article discusses several principles of behavioral economics, including inertia, loss aversion, choice overload, and relative social ranking. Whereas these principles have been applied to motivate personal health decisions, retirement planning, and savings behavior, they have been largely ignored in the design of physician incentive programs. Applying these principles to physician incentives can improve their effectiveness through better alignment with performance goals. Anecdotal examples of successful incentive programs that apply behavioral economics principles are provided, even as the authors recognize that its application to the design of physician incentives is largely untested, and many outstanding questions exist. Application and rigorous evaluation of infrastructure changes and incentives are needed to design payment systems that incentivize high-quality, cost-conscious care.

Wireless Medical Telemetry Service Is Changing, Not Going Away.

The Wireless Medical Telemetry Service (WMTS) was established in 1999 by the Federal Communications Commission (FCC) to protect the use of licensed medical telemetry for physiological and fetal monitoring. The WMTS space has three frequency bands: 608-614 MHz (over-the-air [OTA] television channel 37), 1,395-1,400 MHz, and 1,427-1,432 MHz. This article addresses the recent FCC rule affecting the OTA channel 37 WMTS band. We also will address the potential impact on WMTS use in the hospital, the potential risks, and what hospitals need to do to mitigate those risks.

White matter hyperintensities and hypobaric exposure.

OBJECTIVE: Demonstrate that occupational exposure to nonhypoxic hypobaria is associated with subcortical white matter hyperintensities (WMHs) on fluid-attenuated inversion recovery magnetic resonance imaging (MRI). METHODS: Eighty-three altitude chamber personnel (PHY), 105 U-2 pilots (U2P), and 148 age- controlled and health-matched doctorate degree controls (DOC) underwent high-resolution MRI. Subcortical WMH burden was quantified as count and volume of subcortical WMH lesions after transformation of images to the Talairach atlas-based stereotactic frame. RESULTS: Subcortical WMHs were more prevalent in PHY (volume p = 0.011/count p = 0.019) and U2P (volume p < 0.001/count p < 0.001) when compared to DOC, whereas PHY were not significantly different than U2P. INTERPRETATION: This study provides strong evidence that nonhypoxic hypobaric exposure may induce subcortical WMHs in a young, healthy population lacking other risk factors for WMHs and adds this occupational exposure to other environmentally related potential causes of WMHs. Ann Neurol 2014;76:719-726.

Imaging of pediatric pathology during the Iraq and Afghanistan conflicts.

United States Armed Forces radiologists deployed to Afghanistan and Iraq in modern military conflicts may encounter pediatric patients as a casualty of war or when providing humanitarian assistance to the indigenous population. Pediatric patients account for 4-7% of admissions at U.S. military hospitals during the Iraq and Afghanistan conflicts. It is pertinent for radiologists in the humanitarian care team to be familiar with imaging pediatric trauma patients, the pathology endemic to the local population, and delayed presentations of congenital and developmental disorders to adequately care for these patients. The radiological manifestations of various pediatric disorders seen in the setting of the Iraq and Afghanistan conflicts will be explored.

Results of a pilot randomised controlled trial to measure the clinical and cost effectiveness of peer support in increasing hope and quality of life in mental health patients discharged from hospital in the UK.

BACKGROUND: Mental health patients can feel anxious about losing the support of staff and patients when discharged from hospital and often discontinue treatment, experience relapse and readmission to hospital, and sometimes attempt suicide. The benefits of peer support in mental health services have been identified in a number of studies with some suggesting clinical and economic gains in patients being discharged. METHODS: This pilot randomised controlled trial with economic evaluation aimed to explore whether peer support in addition to usual aftercare for patients during the transition from hospital to home would increase hope, reduce loneliness, improve quality of life and show cost effectiveness compared with patients receiving usual aftercare only, with follow-up at one and three-months post-discharge. RESULTS: A total of 46 service users were recruited to the study; 23 receiving peer support and 23 in the care-as-usual arm. While this pilot trial found no statistically significant benefits for peer support on the primary or secondary outcome measures, there is an indication that hope may be further increased in those in receipt of peer support. The total cost per case for the peer support arm of the study was £2154 compared to £1922 for the control arm. The mean difference between costs was minimal and not statistically significant. However, further analyses demonstrated that peer support has a reasonably high probability of being more cost effective for a modest positive change in the measure of hopelessness. Challenges faced in recruitment and follow-up are explored alongside limitations in the delivery of peer support. CONCLUSIONS: The findings suggest there is merit in conducting further research on peer support in the transition from hospital to home consideration should be applied to the nature of the patient population to whom support is offered; the length and frequency of support provided; and the contact between peer supporters and mental health staff. There is no conclusive evidence to support the cost effectiveness of providing peer support, but neither was it proven a costly intervention to deliver. The findings support an argument for a larger scale trial of peer support as an adjunct to existing services. TRIAL REGISTRATION: Current Controlled Trials ISRCTN74852771.

Relative Severity of Human Performance Decrements Recorded in Rapid vs. Gradual Decompression.

INTRODUCTION: Cabin decompression presents a threat in high-altitude-capable aircraft. A chamber study was performed to compare effects of rapid (RD) vs. gradual decompression and gauge impairment at altitude with and without hypoxia, as well as to assess recovery.METHODS: There were 12 participants who completed RD (1 s) and Gradual (3 min 12 s) ascents from 2743-7620 m (9000-25000 ft) altitude pressures while breathing air or 100% O2. Physiological indices included oxygen saturation (SPo2), heart rate (HR), respiration, end tidal O2 and CO2 partial pressures, and electroencephalography (EEG). Cognition was evaluated using SYNWIN, which combines memory, arithmetic, visual, and auditory tasks. The study incorporated ascent rate (RD, gradual), breathing gas (air, 100% O2) and epoch (ground-level, pre-breathe, ascent-altitude, recovery) as factors.RESULTS: Physiological effects in hypoxic "air" ascents included decreased SPo2 and end tidal O2 and CO2 partial pressures (hypocapnia), with elevated HR and minute ventilation (V˙E); SPo2 and HR effects were greater after RD (-7.3% lower and +10.0 bpm higher, respectively). HR and V˙E decreased during recovery. SYNWIN performance declined during ascent in air, with key metrics, including composite score, falling further (-75% vs. -50%) after RD. Broad cognitive impairment was not recorded on 100% O2, nor in recovery. EEG signals showed increased slow-wave activity during hypoxia.DISCUSSION: In hypoxic exposures, RD impaired performance more than gradual ascent. Hypobaria did not comprehensively impair performance without hypoxia. Lingering impairment was not observed during recovery, but HR and V˙E metrics suggested compensatory slowing following altitude stress. Participants' cognitive strategy shifted as hypoxia progressed, with efficiency giving way to "satisficing," redistributing effort to easier tasks.Beer J, Mojica AJ, Blacker KJ, Dart TS, Morse BG, Sherman PM. Relative severity of human performance decrements recorded in rapid vs. gradual decompression. Aerosp Med Hum Perform. 2024; 95(7):353-366.

Cerebral oxygenation and perfusion kinetics monitoring of military aircrew at high G using novel fNIRS wearable system.

Introduction: Real-time physiological episode (PE) detection and management in aircrew operating high-performance aircraft (HPA) is crucial for the US Military. This paper addresses the unique challenges posed by high acceleration (G-force) in HPA aircrew and explores the potential of a novel wearable functional near-infrared spectroscopy (fNIRS) system, named NIRSense Aerie, to continuously monitor cerebral oxygenation during high G-force exposure. Methods: The NIRSense Aerie system is a flight-optimized, wearable fNIRS device designed to monitor tissue oxygenation 13-20 mm below the skin's surface. The system includes an optical frontend adhered to the forehead, an electronics module behind the earcup of aircrew helmets, and a custom adhesive for secure attachment. The fNIRS optical layout incorporates near-distance, middle-distance, and far-distance infrared emitters, a photodetector, and an accelerometer for motion measurements. Data processing involves the modified Beer-Lambert law for computing relative chromophore concentration changes. A human evaluation of the NIRSense Aerie was conducted on six subjects exposed to G-forces up to +9 Gz in an Aerospace Environmental Protection Laboratory centrifuge. fNIRS data, pulse oximetry, and electrocardiography (HR) were collected to analyze cerebral and superficial tissue oxygenation kinetics during G-loading and recovery. Results: The NIRSense Aerie successfully captured cerebral deoxygenation responses during high G-force exposure, demonstrating its potential for continuous monitoring in challenging operational environments. Pulse oximetry was compromised during G-loading, emphasizing the system's advantage in uninterrupted cerebrovascular monitoring. Significant changes in oxygenation metrics were observed across G-loading levels, with distinct responses in Deoxy-Hb and Oxy-Hb concentrations. HR increased during G-loading, reflecting physiological stress and the anti-G straining maneuver. Discussion: The NIRSense Aerie shows promise for real-time monitoring of aircrew physiological responses during high G-force exposure. Despite challenges, the system provides valuable insights into cerebral oxygenation kinetics. Future developments aim for miniaturization and optimization for enhanced aircrew comfort and wearability. This technology has potential for improving anti-G straining maneuver learning and retention through real-time cerebral oxygenation feedback during centrifuge training.

Spatial and temporal escape from fungal parasitism in natural communities of anciently asexual bdelloid rotifers.

Sexual reproduction is costly, but it is nearly ubiquitous among plants and animals, whereas obligately asexual taxa are rare and almost always short-lived. The Red Queen hypothesis proposes that sex overcomes its costs by enabling organisms to keep pace with coevolving parasites and pathogens. If so, the few cases of stable long-term asexuality ought to be found in groups whose coevolutionary interactions with parasites are unusually weak. In theory, antagonistic coevolution will be attenuated if hosts disperse among patches within a metapopulation separately from parasites and more rapidly. We examined whether these conditions are met in natural communities of bdelloid rotifers, one of the longest-lived asexual lineages. At any life stage, these microscopic invertebrates can tolerate the complete desiccation of their ephemeral freshwater habitats, surviving as dormant propagules that are readily carried by the wind. In our field experiments, desiccation and wind transport enabled bdelloids to disperse independently of multiple fungal parasites, in both time and space. Surveys of bdelloid communities in unmanipulated moss patches confirmed that fungal parasitism was negatively correlated with extended drought and increasing height (exposure to wind). Bdelloid ecology therefore matches a key condition of models in which asexuals persist through spatio-temporal decoupling from coevolving enemies.

Patient safety trilogy: perspectives from clinical engineering.

This article examines the role a clinical engineering or healthcare technology management (HTM) department can play in promoting patient safety from three different perspectives: a community hospital, a national government health system, and an academic medical center. After a general overview, Izabella Gieras from Huntington Hospital in Pasadena, CA, leads off by examining the growing role of human factors in healthcare technology, and describing how her facility uses clinical simulations in medical equipment evaluations. A section by Paul Sherman follows, examining patient safety initiatives from the perspective of the Veterans Health Administration with a focus on hazard alerts and recalls. Dennis Minsent from Oregon Health & Science University writes about patient safety from an academic healthcare perspective, and details how clinical engineers can engage in multidisciplinary safety opportunities.

Lingering Altitude Effects During Piloting and Navigation in a Synthetic Cockpit.

INTRODUCTION: A study was performed to evaluate a cockpit flight simulation suite for measuring moderate altitude effects in a limited subject group. Objectives were to determine whether the apparatus can detect subtle deterioration, record physiological processes throughout hypobaric exposure, and assess recovery.METHODS: Eight subjects trained to perform precision instrument control (PICT) flight and unusual attitude recovery (UAR) and completed chamber flights dedicated to the PICT and UAR, respectively. Each flight comprised five epochs, including ground level pressure (GLP), ascent through altitude plateaus at 10,000, 14,000, and 17,500 ft (3050, 4270, and 5338 m), then postexposure recovery. PICT performance was assessed using control error (FSE) and time-out-of-bounds (TOOB) when pilots exited the flight corridor. UARs were assessed using response times needed to initiate correction and to achieve wings-level attitude. Physiological indices included Spo2, heart rate (HR), end tidal O2 and CO2 pressures, and respiration metrics.RESULTS: Seven subjects completed both flights. PICT performance deteriorated at altitude: FSE increased 33% at 17,513 ft and 21% in Recovery vs. GLP. Mean TOOB increased from 11 s at GLP to 60 s in Recovery. UAR effects were less clear, with some evidence of accelerated responses during and after ascent.CONCLUSIONS: The test paradigm was shown to be effective; piloting impairment was detected during and after exposure. Physiological channels recorded a combination of hypoxia, elevated ventilation, and hypocapnia during ascent, followed by respiratory slowing in recovery. Findings indicate precision piloting and respiration are subject to changes during moderate altitude exposure and may remain altered after Spo2 recovers, and changes may be linked to hypocapnia.Beer J, Morse B, Dart T, Adler S, Sherman P. Lingering altitude effects during piloting and navigation in a synthetic cockpit. Aerosp Med Hum Perform. 2023; 94(3):135-141.

Hyperintense white matter lesions in 50 high-altitude pilots with neurologic decompression sickness.

INTRODUCTION: Neurologic decompression sickness (NDCS) can affect high-altitude pilots, causing variable central nervous system symptoms. Five recent severe episodes prompted further investigation. METHODS: We report the hyperintense white matter (HWM) lesion imaging findings in 50 U-2 pilot volunteers, and compare 12 U-2 pilots who experienced clinical NDCS to 38 U-2 pilots who did not. The imaging data were collected using a 3T magnetic resonance imaging scanner and high-resolution (1-mm isotropic) three-dimensional fluid-attenuated inversion recovery sequence. Whole-brain and regional lesion volume and number were compared between groups. RESULTS: The NDCS group had significantly increased whole brain and insular volumes of HWM lesions. The intergroup difference in lesion numbers was not significant. CONCLUSION: A clinical episode of NDCS was associated with a significant increase in HWM lesion volume, especially in the insula. We postulate this to be due to hypobaric exposure rather than hypoxia since all pilots were maintained on 100% oxygen throughout the flight. Further studies will be necessary to better understand the pathophysiology underlying these lesions.

High altitude is associated with pTau deposition, neuroinflammation, and myelin loss.

Mammals are able to adapt to high altitude (HA) if appropriate acclimation occurs. However, specific occupations (professional climbers, pilots, astronauts and other) can be exposed to HA without acclimation and be at a higher risk of brain consequences. In particular, US Air Force U2-pilots have been shown to develop white matter hyperintensities (WMH) on MRI. Whether WMH are due to hypoxia or hypobaria effects is not understood. We compared swine brains exposed to 5000 feet (1524 m) above sea level (SL) with 21% fraction inspired O2 (FiO2) (Control group [C]; n = 5) vs. 30,000 feet (9144 m) above SL with 100% FiO2 group (hypobaric group [HYPOBAR]; n = 6). We performed neuropathologic assessments, molecular analyses, immunohistochemistry (IHC), Western Blotting (WB), and stereology analyses to detect differences between HYPOBAR vs. Controls. Increased neuronal insoluble hyperphosphorylated-Tau (pTau) accumulation was observed across different brain regions, at histological level, in the HYPOBAR vs. Controls. Stereology-based cell counting demonstrated a significant difference (p < 0.01) in pTau positive neurons between HYPOBAR and C in the Hippocampus. Higher levels of soluble pTau in the Hippocampus of HYPOBAR vs. Controls were also detected by WB analyses. Additionally, WB demonstrated an increase of IBA-1 in the Cerebellum and a decrease of myelin basic protein (MBP) in the Hippocampus and Cerebellum of HYPOBAR vs. Controls. These findings illustrate, for the first time, changes occurring in large mammalian brains after exposure to nonhypoxic-hypobaria and open new pathophysiological views on the interaction among hypobaria, pTau accumulation, neuroinflammation, and myelination in large mammals exposed to HA.

Monitoring of SARS-CoV-2 in sewersheds with low COVID-19 cases using a passive sampling technique.

Monitoring SARS-CoV-2 RNA in sewer systems, upstream of a wastewater treatment plant, is an effective approach for understanding potential COVID-19 transmission in communities with higher spatial resolutions. Passive sampling devices provide a practical solution for frequent sampling within sewer networks where the use of autosamplers is not feasible. Currently, the design of upstream sampling is impeded by limited understanding of the fate of SARS-CoV-2 RNA in sewers and the sensitivity of passive samplers for the number of infected individuals in a catchment. In this study, passive samplers containing electronegative membranes were applied for at least 24-h continuous sampling in sewer systems. When monitoring SARS-CoV-2 along a trunk sewer pipe, we found RNA signals decreased proportionally to increasing dilutions, with non-detects occurring at the end of pipe. The passive sampling membranes were able to detect SARS-CoV-2 shed by >2 COVID-19 infection cases in 10,000 people. Moreover, upstream monitoring in multiple sewersheds using passive samplers identified the emergence of SARS-CoV-2 in wastewater one week ahead of clinical reporting and reflected the spatiotemporal spread of a COVID-19 cluster within a city. This study provides important information to guide the development of wastewater surveillance strategies at catchment and subcatchment levels using different sampling techniques.

SARS-CoV-2 RNA monitoring in wastewater as a potential early warning system for COVID-19 transmission in the community: A temporal case study.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus which causes coronavirus disease (COVID-19), has spread rapidly across the globe infecting millions of people and causing significant health and economic impacts. Authorities are exploring complimentary approaches to monitor this infectious disease at the community level. Wastewater-based epidemiology (WBE) approaches to detect SARS-CoV-2 RNA in municipal wastewater are being implemented worldwide as an environmental surveillance approach to inform health authority decision-making. Owing to the extended excretion of SARS-CoV-2 RNA in stool, WBE can surveil large populated areas with a longer detection window providing unique information on the presence of pre-symptomatic and asymptomatic cases that are unlikely to be screened by clinical testing. Herein, we analysed SARS-CoV-2 RNA in 24-h composite wastewater samples (n = 63) from three wastewater treatment plants (WWTPs) in Brisbane, Queensland, Australia from 24th of February to 1st of May 2020. A total of 21 samples were positive for SARS-CoV-2, ranging from 135 to 11,992 gene copies (GC)/100 mL of wastewater. Detections were made in a Southern Brisbane WWTP in late February 2020, up to three weeks before the first clininal case was reported there. Wastewater samples were generally positive during the period with highest caseload data. The positive SARS-CoV-2 RNA detection in wastewater while there were limited clinical reported cases demonstrates the potential of WBE as an early warning system to identify hotspots and target localised public health responses, such as increased individual testing and the provision of health warnings.

Apolipoprotein E promoter genotypes are not associated with white matter hyperintensity development in high-altitude careers.

OBJECTIVE: This study sought to determine if there is an association between variants in the apolipoprotein E (ApoE) promoter regions and development of white matter hyperintensities (WMH) in military subjects who have been exposed to high altitude. In an earlier study, we found that ApoE status did not correlate with WMH development, and here we hypothesized that regulation of APOE protein expression may be protective. RESULTS: Our cohort of 92 subjects encountered altitude exposures above 25,000 feet mean sea level through their occupations as pilots or altitude chamber technicians. Using Taqman-style polymerase chain reaction genotyping and t-tests and two-way analyses of variance we found no significant association between ApoE promoter genotypes and the presence, volume, or quantity of WMHs after high altitude exposure. Taken together, the observations that neither ApoE genotype status nor promoter status are associated with WMH properties, we believe that the mechanism of action for developing WMH does not derive from ApoE, nor would therapies for ApoE-mediated neurodegeneration likely benefit high altitude operators.

Replicability of Neural and Behavioral Measures of Tinnitus Handicap in Civilian and Military Populations: Preliminary Results.

Purpose In the past decade, resting-state functional connectivity, acquired using functional magnetic resonance imaging (fMRI), has emerged as a popular measure of tinnitus, especially as related to self-reported handicap or psychological reaction. The goal of this study was to assess replicability of neural correlates of tinnitus, namely, resting-state functional connectivity, in the same individuals acquired over 2 sessions. Method Data were collected at 2 different sites (University of Illinois at Urbana-Champaign and Joint Base San Antonio Wilford Hall Ambulatory Surgical Center) using similar 3T magnets and similar data acquisition paradigms. Thirty-six patients (all civilians) were scanned using resting-state fMRI at the University of Illinois at Urbana-Champaign. Ten patients, active-duty Service members and Veterans, were scanned at the Wilford Hall Ambulatory Surgical Center and the Department of Defense Hearing Center of Excellence. Each participant was scanned twice, a week apart, using identical protocols of 10 min resting-state fMRI. Results Tinnitus handicap scores using the Tinnitus Functional Index and the Tinnitus Primary Function Questionnaire ranged between no or mild handicap to moderately severe handicap but did not significantly differ between visits. We examined the default mode, dorsal attention, and auditory resting-state networks and found that the strength of the within-network functional connections across visit was similar for the attention and default mode networks but not for the auditory network. In addition, the functional connection between the attention network and precuneus, a region of the default mode network, was also replicable across visits. Conclusions Our results show that resting-state fMRI measures are replicable and reliable in patients with a subjective condition, although some networks and functional connections may be more stable than others. This paves the way for using resting-state fMRI to measure the efficacy of tinnitus interventions and as a tool to help propose better management options.

Morning sickness: adaptive cause or nonadaptive consequence of embryo viability?

"Morning sickness" is the common term for nausea and vomiting in early human pregnancy (NVP). Recent interest in why NVP occurs-that is, in the evolutionary costs and benefits of NVP-has spurred the development of two alternative hypotheses. The "prophylaxis," or "maternal and embryonic protection," hypothesis suggests that NVP serves a beneficial function by expelling foods that may contain harmful toxins and microorganisms and triggering aversions to such foods throughout pregnancy. The alternative "by-product" hypothesis suggests that NVP is a nonfunctional by-product of conflict--over resource allocation--between the pregnant woman and the embryo. The critical predictions of the prophylaxis hypothesis have been developed and tested, whereas the by-product hypothesis has not been subjected to similar scrutiny. To address this gap, we developed a graphical model and used it to derive predictions from the by-product hypothesis under two different assumptions, namely, that NVP is either (i) a by-product of current conflict between a pregnant woman and an embryo or (ii) a by-product of honest signals of viability produced by the embryo. Neither version of the by-product hypothesis is fully consistent with available data. By contrast, the timing of NVP, its variation among societies, and associated patterns of food cravings and aversions are consistent with the prophylaxis hypothesis.